Crystal structure of a copper(II)–famotidine complex and solution studies of the Cu2+–famotidine–histidine ternary system

The crystal structure of the complex [CuL][ClO4]2(L = 3-{[2-diaminomethyleneamino)thiazol-4-yl]methylsulfanyl}-N2-sulfamoylpropionamidine, famotidine) has been determined. It provides a full description of the metal binding sites and reveals the impact of metal co-ordination on the conformation of the drug molecule. Even metal ion binding is not able to change some conformational features of famotidine, which could be an important factor biologically. Potentiometric and spectroscopic data were obtained for the ternary species in the Cu2+–famotidine–histidine system and show that famotidine is a very competitive chelating agent even in the presence of the strongly co-ordinating amino acid.

[1]  T. Kupka,et al.  Histamine H2 antagonists: powerful ligands for copper(II). Reinterpretation of the famotidine–copper(II) system , 1995 .

[2]  P. Decock,et al.  The binding ability of famotidine, the antiulcerogenic agent. Ternary complexes with histidine and histamine with copper(II) , 1993 .

[3]  E. Bouwman,et al.  Model systems for type I copper proteins: structures of copper coordination compounds with thioether and azole-containing ligands , 1990 .

[4]  G. Sheldrick.  Phase annealing in SHELX-90: direct methods for larger structures , 1990 .

[5]  E. Bouwman,et al.  Copper co-ordination compounds of a chelating imidazole–thioether ligand. The molecular structures of [1,3-bis(5-methyl-4-imidazolyl)-2-thiapropane]-bis(nitrato)copper(II) and bis[1,3-bis(5-methyl-4-imidazolyl)-2-thiapropane]-copper(II) bis(tetrafluoroborate)–ethanol(1/2) , 1990 .

[6]  T. Ishida,et al.  Structural study of histamine H2-receptor antagonists. Five 3-[2-(diamino-methyleneamino)-4-thiazolylmethylthio]propionamidine and -amide derivatives. , 1989, Acta crystallographica. Section B, Structural science.

[7]  L. Golič,et al.  Structure of a new crystalline form of famotidine , 1989 .

[8]  T. Ishida,et al.  On the structure-activity relationship of histamine H2-receptor antagonists based on the X-ray crystal structures and 1H-NMR spectra of amidine derivatives. , 1987, Molecular pharmacology.

[9]  P. Gans,et al.  SUPERQUAD: an improved general program for computation of formation constants from potentiometric data , 1985 .

[10]  C. R. Ganellin,et al.  Pharmacology of Histamine Receptors , 1982 .

[11]  E. Deutsch,et al.  Coordination stabilization of organic intermediates. Crystal structure of {[(en)2Co(SCH2CH2NH2)]2I}(NO3)5.4H2O, a stable complex of iodine(I) , 1980 .

[12]  H. Irving,et al.  A study of some problems in determining the stoicheiometric proton dissociation constants of complexes by potentiometric titrations using a glass electrode , 1967 .